CN115975238A - Ethylene diamine tetraacetic acid modified membrane type artificial organ material and preparation method thereof - Google Patents
Ethylene diamine tetraacetic acid modified membrane type artificial organ material and preparation method thereof Download PDFInfo
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Landscapes
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention discloses an Ethylene Diamine Tetraacetic Acid (EDTA) modified membrane type artificial organ material and a preparation method thereof, belonging to the technical field of medicines. The preparation method of the ethylene diamine tetraacetic acid modified membrane type artificial organ material comprises the following steps: constructing a basement membrane of a membrane type artificial organ; (2) Preparing an ethylene diamine tetraacetic acid modified membrane type artificial organ material: carrying out oxygen plasma treatment on the base film obtained in the step (1), and fully dip-coating the base film subjected to the oxygen plasma treatment in 0.1mol/L EDTA solution for 12-24 h; and (3) soaking and cleaning with deionized water, and drying to obtain the ethylenediamine tetraacetic acid modified membrane type artificial viscera material. The EDTA modified membrane has good effects of resisting blood coagulation, chelating heavy metals and other toxicants, and can inhibit the formation of bacterial biofilms on the membrane surface, thereby reducing the infection risk of membrane type artificial viscera patients; the preparation method has simple steps and is suitable for industrial batch production.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an Ethylene Diamine Tetraacetic Acid (EDTA) modified membrane type artificial organ material and a preparation method thereof.
Background
The membrane type artificial organs such as extracorporeal membrane lung oxygenation, artificial liver, blood perfusion adsorption, plasma replacement and the like are widely applied to critical patients such as systemic inflammatory response syndrome, multi-organ failure, acute poisoning and the like. However, membrane-type artificial organs belong to extracorporeal materials, and inevitably activate the blood coagulation system after contacting with blood, finally cause membrane-related thrombosis, and influence the treatment effect. Therefore, the anticoagulation modification of the membrane type artificial visceral organ material is always a difficult point which needs to be broken through urgently in clinic.
There is currently a great deal of research on the inhibition of thrombin or platelets to achieve the goals of regional anticoagulation and anti-thrombosis on membranes, but little attention has been paid to Ca during membrane-associated thrombosis 2+ Plays an important role. In the intrinsic coagulation pathway, ca 2+ Can help to activate factor XI, and together with factor VIII and activated factor IX, activate factor X. In the extrinsic coagulation pathway, ca 2+ Together with tissue factor, factor VII, activates factor X. In a common pathway, fibrinogen can be converted to fibrin monomers, along with factor V, activated factor X. In addition, it may also assist in activating factor XIII and continue to assist factor XIII in converting soluble fibrin monomers into stable fibrin polymers. In view of Ca 2+ Are indispensable in each coagulation pathway and therefore antagonize Ca 2+ Can be used as a new target of anti-membrane material thrombus.
On the other hand, acute poisoning has the characteristics of sudden change, complex disease condition and the like, and severe patients can have multiple organ dysfunction or failure and even possibly endanger the life of patients. At present, the membrane type artificial organ is gradually widely applied to the treatment of acute poisoning patients, can directly and quickly remove poison from blood by means of extracorporeal blood circulation, and stops the toxic action of the poison on target organs of organisms, so that the poisoning symptom is quickly relieved or relieved, and the cure success rate is improved. However, at present, there are few membrane materials which can simultaneously achieve antithrombotic effect and acute poisoning treatment.
Ethylene diamine tetraacetic acid (EDTA, formula I) can effectively chelate Ca in blood 2+ Thereby stopping the coagulation process of endogenous, exogenous and common routes and preventing the formation of thrombus. Meanwhile, EDTA is used as a metal chelating medicament with excellent curative effect, can reduce organ injury caused by heavy metal poisoning, and researches show that EDTA also plays a role in reducing organ injury in the treatment process of paraquat pesticide poisoning. However, there is no EDTA-modified membrane-type artificial organ material.
Disclosure of Invention
The invention aims to provide an ethylene diamine tetraacetic acid modified membrane type artificial visceral organ material and a preparation method thereof. Aims to solve the problems of blood coagulation and bacterial infection in the process of using the membrane type artificial organ to treat critically ill patients. In view of the advantages of EDTA such as antithrombotic property, poison removal and antibacterial property, EDTA is used for modifying the membrane material so as to play a role in anticoagulation and antibiosis during the treatment of critical patients by using the membrane type artificial viscera; meanwhile, due to the toxic removing characteristic of EDTA, the modified membrane can play an excellent treatment effect on the treatment of patients suffering from acute heavy metal and pesticide poisoning; the prepared ethylene diamine tetraacetic acid modified membrane type artificial visceral organ material can treat acute poisoning and has a bacteriostatic function while effectively resisting blood coagulation.
The embodiment of the invention is realized in such a way that a preparation method of an ethylene diamine tetraacetic acid modified membrane type artificial organ material comprises the following steps:
(1) Constructing a basement membrane of the membrane type artificial organ:
dissolving a membrane substrate in a solvent to prepare a solution containing 18-22% of solid content of the membrane substrate, and standing and defoaming to obtain a membrane casting solution; curing the membrane casting solution and then soaking to obtain a base membrane of the membrane type artificial viscera;
(2) Preparing an ethylene diamine tetraacetic acid modified membrane type artificial organ material:
carrying out oxygen plasma treatment on the base film obtained in the step (1), and fully dip-coating the base film subjected to the oxygen plasma treatment in 0.1mol/L EDTA solution for 12-24 h; soaking and cleaning the membrane type artificial viscera material in deionized water, and drying to obtain the ethylenediamine tetraacetic acid modified membrane type artificial viscera material.
The membrane substrate in the step (1) is one or more of a polyether sulfone membrane substrate, a polysulfone membrane substrate, a polyurethane membrane substrate, a cellulose membrane substrate or a polylactic acid membrane substrate.
The solvent in the step (1) is one or more of DMF, DMAC and NMP.
The curing in the step (1) is to put the casting solution with the temperature of 40-60 ℃ into a coagulating bath with the temperature of 25-40 ℃ for curing.
The oxygen plasma treatment in the step (2) specifically comprises the following steps: the base film is put into a cold plasma processor, the use power is adjusted to be 120-180W, and the base film is processed for 10-15 min under the oxygen atmosphere.
The 0.1mol/L EDTA solution in the step (2) is prepared by the following steps: dissolving EDTA in Tris-HCl buffer solution to prepare 0.1mol/L EDTA solution; wherein the pH value of the Tris-HCl buffer solution is 7.5-8.5.
And (3) soaking and cleaning with deionized water in the step (2), specifically, soaking and cleaning for 1 hour with deionized water. Soaking in deionized water for 1h for cleaning can ensure complete cleaning of EDTA which is not stably soaked on the surface of the membrane.
An ethylenediamine tetraacetic acid modified membrane type artificial organ material is obtained by the preparation method.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
1. at present, the modification of membrane type artificial organs in the prior art is mainly to increase the anticoagulation performance, but the research on membrane materials for relieving organ injuries of heavy metal and pesticide poisoning patients is less, and particularly, no membrane materials capable of resisting thrombus and treating acute poisoning are developed. The EDTA modified membrane has good effects of anticoagulation, heavy metal chelation and other toxicants, and can inhibit the formation of bacterial biofilms on the membrane surface, thereby reducing the infection risk of membrane type artificial viscera patients.
2. The preparation method of the ethylenediamine tetraacetic acid modified membrane type artificial visceral organ material has simple steps, can complete modification in only two steps, and is suitable for industrial batch production.
3. The water contact angle of the ethylene diamine tetraacetic acid modified membrane type artificial organ material obtained by the invention is obviously reduced, the surface thrombus adhesion of the membrane can be effectively reduced, the bacteriostatic rate is higher than that of an unmodified common membrane, and the antibacterial effect is good.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. In addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention.
At present, the problems of blood coagulation, bacterial infection and the like exist in the process of using membrane type artificial organ therapy for critically ill patients. In order to solve the technical problems, the invention provides an ethylene diamine tetraacetic acid modified membrane type artificial organ material and a preparation method thereof. In view of the advantages of EDTA such as antithrombotic property, poison removal and antibacterial property, EDTA is used for modifying the membrane material so as to play a role in anticoagulation and antibiosis during the treatment of critical patients by using the membrane type artificial viscera; meanwhile, due to the toxic removing characteristic of EDTA, the modified membrane can play an excellent treatment effect on the treatment of patients suffering from acute heavy metal and pesticide poisoning; the prepared ethylene diamine tetraacetic acid modified membrane type artificial visceral organ material can treat acute poisoning and has a bacteriostatic function while effectively resisting blood coagulation.
Example one
A preparation method of an ethylene diamine tetraacetic acid modified membrane type artificial organ material comprises the following steps:
(1) Constructing a basement membrane of the membrane type artificial organ:
dissolving a membrane substrate (polyether sulfone membrane substrate) in a solvent (DMF) to prepare a solution containing 20% of the solid content of the substrate, and standing and defoaming to obtain a membrane casting solution; placing the casting solution at 50 ℃ in a coagulating bath at 30 ℃, curing and soaking to obtain a polyether sulfone film substrate base film;
(2) Preparation of EDTA-modified membrane-type artificial organ material:
carrying out oxygen plasma treatment on the base film, putting the base film into a cold plasma treatment instrument, adjusting the use power to be 150W, and treating for 12min in an oxygen atmosphere; dissolving EDTA in Tris-HCl buffer solution (pH = 7.5-8.5) to prepare 0.1mol/L EDTA solution, and fully dip-coating the base membrane in the solution for 18h; and then soaking the modified membrane in deionized water for 1h to ensure that EDTA which is not stably soaked on the membrane surface is completely cleaned, and drying the membrane after complete cleaning to obtain the EDTA modified membrane type artificial organ material (namely the EDTA modified polyether sulfone membrane type artificial organ material).
Example two
A preparation method of an ethylene diamine tetraacetic acid modified membrane type artificial organ material comprises the following steps:
(1) Constructing a basement membrane of a membrane type artificial organ:
dissolving a membrane substrate (polysulfone) in a solvent (DMAC) to prepare a solution containing 18% of the solid content of the substrate, and standing and defoaming to obtain a membrane casting solution; placing the casting solution at 40 ℃ in a coagulating bath at 25 ℃, curing and soaking to obtain a base film;
(2) Preparation of EDTA-modified membrane-type artificial organ material:
carrying out oxygen plasma treatment on the base film, putting the base film into a cold plasma treatment instrument, adjusting the use power to be 120W, and treating for 15min in an oxygen atmosphere; dissolving EDTA in Tris-HCl buffer solution (pH = 7.5-8.5) to prepare 0.1mol/L EDTA solution, and fully dip-coating the base membrane in the solution for 24 hours; and then soaking the modified membrane in deionized water for 1 hour to ensure that EDTA which is not stably soaked on the membrane surface is completely cleaned, and drying the EDTA after complete cleaning to obtain the EDTA modified membrane type artificial organ material.
EXAMPLE III
A preparation method of an ethylene diamine tetraacetic acid modified membrane type artificial organ material comprises the following steps:
(1) Constructing a basement membrane of a membrane type artificial organ:
dissolving a membrane substrate (polylactic acid) in a solvent (NMP) to prepare a solution containing 22% of the solid content of the substrate, and standing and defoaming to obtain a membrane casting solution; placing the casting solution at 60 ℃ in a coagulating bath at 40 ℃, and soaking after solidification to obtain a base film;
(2) Preparation of EDTA-modified membrane-type artificial organ material:
carrying out oxygen plasma treatment on the base film, putting the base film into a cold plasma treatment instrument, adjusting the use power to be 180W, and treating for 10min in an oxygen atmosphere; dissolving EDTA in Tris-HCl buffer solution (pH = 7.5-8.5) to prepare 0.1mol/L EDTA solution, and fully dip-coating the base membrane in the solution for 12 hours; and then soaking the modified membrane in deionized water for 1h to ensure that EDTA which is not stably soaked on the surface of the membrane is completely cleaned, and drying the membrane after complete cleaning to obtain the EDTA modified membrane type artificial visceral organ material.
Compared with the prior art, the invention has the following beneficial effects:
the EDTA modified membrane type artificial organ material prepared by the method in the first to third embodiments of the invention can prevent membrane material related thrombosis caused by extracorporeal membrane lung oxygenation, artificial liver, blood perfusion adsorption, plasma replacement and the like, is particularly suitable for treating patients suffering from acute poisoning, and has an antibacterial effect. The method has simple steps, can be used for industrial batch production, and is suitable for popularization and application.
Comparative example 1
A preparation method of unmodified membrane type artificial organ material comprises the following steps:
(1) Constructing a basement membrane of the membrane type artificial organ:
dissolving a membrane substrate (polyether sulfone membrane substrate) in a solvent (DMF) to prepare a solution containing 20% of the solid content of the substrate, and standing and defoaming to obtain a membrane casting solution; and (3) placing the casting membrane liquid at 50 ℃ in a coagulating bath at 30 ℃, solidifying and soaking to obtain the unmodified polyether sulfone membrane type artificial organ material.
The hydrophilic performance and the bacteriostasis rate of the unmodified polyethersulfone membrane artificial organ material prepared in the first comparative example and the EDTA-modified polyethersulfone membrane artificial organ material prepared in the first example are detected and compared, and the detection results are shown in Table 1.
Table 1 comparison of hydrophilic properties and bacteriostatic ratio of comparative example-polyethersulfone membrane and example-EDTA-modified membrane
The water contact angle is an important performance index for evaluating the blood compatibility of the membrane type artificial organ material, and the membrane material with good blood compatibility can effectively reduce the surface thrombus adhesion. The smaller the water contact angle, the better the blood compatibility of the membrane material. The water contact angle of the EDTA modified polyether sulfone membrane type artificial organ material in the table 1 is obviously lower than that of the common unmodified polyether sulfone membrane type artificial organ material, which indicates that the modified polyether sulfone membrane type artificial organ material can effectively inhibit the formation of membrane thrombus. Meanwhile, the bacteriostasis rate test shows that the bacteriostasis rate of the EDTA modified polyether sulfone membrane type artificial organ material is higher than that of the common polyether sulfone membrane type artificial organ material, which indicates that the EDTA modified membrane type artificial organ material has good bacteriostasis.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
1. at present, the modification of membrane type artificial organs in the prior art is mainly to increase the anticoagulation performance, but the research on membrane materials for relieving organ injury of heavy metal and pesticide poisoning patients is less, and particularly, no membrane materials capable of resisting thrombus and treating acute poisoning are developed. The EDTA modified membrane has good effects of anticoagulation, heavy metal chelation and other toxicants, and can inhibit the formation of bacterial biofilms on the membrane surface, thereby reducing the infection risk of membrane type artificial viscera patients.
2. The preparation method of the ethylenediamine tetraacetic acid modified membrane type artificial visceral organ material has simple steps, can complete modification in only two steps, and is suitable for industrial batch production.
3. The water contact angle of the ethylene diamine tetraacetic acid modified membrane type artificial organ material obtained by the invention is obviously reduced, the thrombus adhesion on the membrane surface can be effectively reduced, the bacteriostasis rate is higher than that of an unmodified common membrane, and the antibacterial effect is good.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (8)
1. A preparation method of an ethylene diamine tetraacetic acid modified membrane type artificial organ material is characterized by comprising the following steps: the method comprises the following steps:
(1) Constructing a basement membrane of a membrane type artificial organ:
dissolving a membrane substrate in a solvent to prepare a solution containing the membrane substrate with the solid content of 18-22%, and standing and defoaming to obtain a membrane casting solution; curing the membrane casting solution and then soaking to obtain a base membrane of the membrane type artificial viscera;
(2) Preparing the ethylene diamine tetraacetic acid modified membrane type artificial organ material:
carrying out oxygen plasma treatment on the base film obtained in the step (1), and fully dip-coating the base film subjected to the oxygen plasma treatment in 0.1mol/L EDTA solution for 12-24 h; soaking and cleaning the membrane type artificial viscera material in deionized water, and drying to obtain the ethylenediamine tetraacetic acid modified membrane type artificial viscera material.
2. The method for preparing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: the membrane substrate in the step (1) is one or more of a polyether sulfone membrane substrate, a polysulfone membrane substrate, a polyurethane membrane substrate, a cellulose membrane substrate or a polylactic acid membrane substrate.
3. The method for preparing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: the solvent in the step (1) is one or more of DMF, DMAC and NMP.
4. The method for preparing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: the curing in the step (1) is to put the casting solution with the temperature of 40-60 ℃ into a coagulating bath with the temperature of 25-40 ℃ for curing.
5. The method for preparing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: the oxygen plasma treatment in the step (2) specifically comprises the following steps: the base film is put into a cold plasma processor, the use power is adjusted to be 120-180W, and the base film is processed for 10-15 min under the oxygen atmosphere.
6. The method for producing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: the 0.1mol/L EDTA solution in the step (2) is prepared by the following steps: dissolving EDTA in Tris-HCl buffer solution to prepare 0.1mol/L EDTA solution; wherein the pH value of the Tris-HCl buffer solution is 7.5-8.5.
7. The method for preparing an ethylenediaminetetraacetic acid-modified membrane-type artificial organ material according to claim 1, wherein: and (3) soaking and cleaning with deionized water in the step (2), specifically, soaking and cleaning for 1 hour with deionized water. The EDTA which is not stably soaked on the surface of the membrane can be completely cleaned by soaking the membrane for 1 hour in deionized water.
8. An ethylenediaminetetraacetic acid-modified membrane-type artificial organ material obtained by the production method according to any one of claims 1 to 7.
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